The aims of this project are to identify the effects of DNA intercalating agents on DNA. The drugs to be studied include anthracycline intercalators and their analogs and non-anthracycline intercalators including aminoanthraquinones. The method to be used will be DNA alkaline elution. A correlation between drug-induced DNA alterations and cytotoxicity will be made utilizing tumor cell cloning. L1210 leukemia cell lines will be used initially. In order to facilitate the understanding of specific mechanisms on the macromolecular level, drug resistant cell lines will also be tested in these systems. The method of DNA alkaline elution will be adapted to use with human tumor specimens and will be assessed for its ability to screen for tumor chemosensitivity. Macromolecular DNA alterations will be correlated with specific classes of DNA intercalating agents. These alterations will be examined for their association with cytotoxicity and their presence in resistant cell lines.